- KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. ... Read More
Safety: Kd vs Vd study
Safety experience
Discontinuation due to adverse reactions and disease progression across treatment arms1,2
Discontinuation due to adverse reactions and disease progression
Safety experience with Kd 56 mg/m2 vs Vd1,2
- Deaths due to adverse reactions within 30 days of the last dose of any therapy in the Kd arm occurred in 7% of patients compared with 5% of patients in the Vd arm1
- The causes of death in patients in the 2 arms (Kd vs Vd) included (n, %): cardiac (4, 1% vs 5, 1%), infections (8, 2% vs 8, 2%), disease progression (7, 2% vs 4, 1%), pulmonary (3, 1% vs 2, < 1%), renal (1, < 1% vs 0, 0%), and other adverse reactions (9, 2% vs 2, < 1%)1
- Dose reductions due to adverse reactions: 23% of patients in the Kd arm experienced dose reductions due to adverse reactions vs 48% in the Vd arm2
Safety profile
Additional safety and clinical considerations1,2
- The overall incidence of cardiac failure events was 11% in the Kd arm versus 3% in the Vd arm1
- The frequency of Grade ≥ 3 cardiac failure events was observed in 5% of Kd patients2
- Death due to cardiac issues occurred in 4 Kd patients vs 5 Vd patients (1% vs 1%)1
Select adverse reactions of interest2
Kd (n = 463) | Vd (n = 456) | |||
---|---|---|---|---|
Preferred term | All grades | Grade ≥ 3 | All grades | Grade ≥ 3 |
Acute renal failure* | 8% | 4% | 5% | 3% |
Cardiac failure† | 8% | 5% | 3% | 2% |
Ischemic heart disease‡ | 3% | 2% | 2% | 2% |
Peripheral neuropathy§ | 19% | 2% | 52% | 8% |
Pulmonary hypertension** | 1% | 1% | 0.2% | 0.2% |
In the Kd arm, the most common treatment-emergent adverse reactions were predominantly Grade 1/21
Most common adverse reactions (≥ 10% in the Kd treatment arm) occurring in months 1-6 of the Kd vs Vd study1
Kd (n = 463) n (%) |
Vd (n = 456) n (%) |
|||
---|---|---|---|---|
Adverse reaction by body system | Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 |
Blood and lymphatic system disorders | ||||
Anemia | 161 (35%) | 57 (12%) | 112 (25%) | 43 (9%) |
Thrombocytopenia* | 125 (27%) | 45 (10%) | 112 (25%) | 64 (14%) |
Gastrointestinal disorders | ||||
Diarrhea | 117 (25%) | 14 (3%) | 149 (33%) | 27 (6%) |
Nausea | 70 (15%) | 4 (1%) | 68 (15%) | 3 (1%) |
Constipation | 60 (13%) | 1 (0%) | 113 (25%) | 6 (1%) |
Vomiting | 45 (10%) | 5 (1%) | 33 (7%) | 3 (1%) |
General disorders and administration site conditions | ||||
Fatigue | 116 (25%) | 14 (3%) | 126 (28%) | 25 (6%) |
Pyrexia | 102 (22%) | 9 (2%) | 52 (11%) | 3 (1%) |
Asthenia | 73 (16%) | 9 (2%) | 65 (14%) | 13 (3%) |
Peripheral edema | 62 (13%) | 3 (1%) | 62 (14%) | 3 (1%) |
Infections and infestations | ||||
Upper respiratory tract infection | 67 (15%) | 4 (1%) | 55 (12%) | 3 (1%) |
Bronchitis | 54 (12%) | 5 (1%) | 25 (6%) | 2 (0%) |
Musculoskeletal and connective tissue disorders | ||||
Muscle spasms | 70 (15%) | 1 (0%) | 23 (5%) | 3 (1%) |
Back pain | 64 (14%) | 8 (2%) | 61 (13%) | 10 (2%) |
Nervous system disorders | ||||
Headache | 67 (15%) | 4 (1%) | 39 (9%) | 2 (0%) |
Peripheral neuropathies† | 56 (12%) | 7 (2%) | 170 (37%) | 23 (5%) |
Psychiatric disorders | ||||
Insomnia | 105 (23%) | 5 (1%) | 116 (25%) | 10 (2%) |
Respiratory, thoracic, and mediastinal disorders | ||||
Dyspnea‡ | 128 (28%) | 23 (5%) | 69 (15%) | 8 (2%) |
Cough§ | 97 (21%) | 0 (0%) | 61 (13%) | 2 (0%) |
Vascular disorders | ||||
Hypertension** | 83 (18%) | 30 (7%) | 33 (7%) | 12 (3%) |
Post hoc analysis at median OS: Kd had comparable exposure-adjusted rates of adverse reactions vs Vd3
The rate of adverse reactions was comparable when adjusted for exposure. Given that patients in the Kd arm received 21 more weeks of treatment than those in the Vd arm, the rate of adverse reactions was adjusted for the different treatment durations.
Exposure-adjusted adverse events
Category | Kd (n = 463) r (95% CI) |
Vd (n = 456) r (95% CI) |
---|---|---|
Any grade AE | 1377 (1256-1509) | 1755 (1600-1925) |
Grade ≥ 3 AE | 164 (148-181) | 178 (160-199) |
Serious AEs | 67.9 (60.3-76.5) | 65.8 (56.9-76.0) |
Grade 5 AE | 5.83 (4.12-8.25) | 5.98 (3.90-9.17) |
Kd resulted in 5x less grade 2 or higher peripheral neuropathy than Vd1
≥ Grade 2 peripheral neuropathy1
Among patients in the Vd group, 82% received subcutaneous Velcade® (bortezomib) throughout their treatment.1
Kd = KYPROLIS®+dexamethasone; Vd = Velcade® (bortezomib)+dexamethasone; r = exposure-adjusted subject rate per 100 subject years; AE = adverse event; OS = overall survival; CI = confidence interval.
Median treatment duration
The median treatment duration was 48 weeks (12 cycles) with Kd vs 27 weeks (8 cycles) with Vd1,6
Median treatment duration (Kd vs Vd)
Select frail-subgroup safety profile (Kd 56 mg/m2 vs Vd)7
SELECT GRADE ≥ 3 TEAEs OF INTEREST
Select grade ≥ 3 TEAEs of interest, n | Kd (n = 168) | Vd (n = 159) |
---|---|---|
Peripheral neuropathy | 4 | 15 |
Acute renal failure | 15 | 7 |
Cardiac failure | 15 | 7 |
Ischemic heart disease | 8 | 6 |
Pulmonary hypertension | 0 | 1 |